Anticonvulsant

Anticonvulsant

Overview
The anticonvulsants are a diverse group of pharmaceuticals
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...

 used in the treatment of epileptic
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...

 seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

s. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain
Neuropathic pain
Neuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...

. The goal of an anticonvulsant is to suppress the rapid and excessive firing of neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s that start a seizure. Failing this, an effective anticonvulsant would prevent the spread of the seizure within the brain and offer protection against possible excitotoxic
Excitotoxicity
Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are...

 effects that may result in brain damage
Brain damage
"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...

.
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Encyclopedia
The anticonvulsants are a diverse group of pharmaceuticals
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...

 used in the treatment of epileptic
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...

 seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

s. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain
Neuropathic pain
Neuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...

. The goal of an anticonvulsant is to suppress the rapid and excessive firing of neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s that start a seizure. Failing this, an effective anticonvulsant would prevent the spread of the seizure within the brain and offer protection against possible excitotoxic
Excitotoxicity
Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are...

 effects that may result in brain damage
Brain damage
"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...

. Some studies have cited that anticonvulsants themselves are linked to lowered IQ in children. However these adverse effects must be balanced against the significant risk epileptiform seizures pose to children and the distinct possibility of death and devastating neurological sequela
Sequela
A sequela) is a pathological condition resulting from a disease, injury, or other trauma.Chronic kidney disease, for example, is sometimes a sequela of diabetes, and neck pain is a common sequela of whiplash or other trauma to the cervical vertebrae. Post-traumatic stress disorder may be a...

 secondary to seizures. Anticonvulsants are more accurately called antiepileptic drugs (abbreviated "AEDs"), sometimes referred to as antiseizure drugs. While an anticonvulsant is a fair description of AEDs, it neglects to differentiate the difference between convulsions and epilepsy. Convulsive non-epileptic seizures
Non-epileptic seizures
Non-epileptic seizures are paroxysmal events that mimic an epileptic seizure but do not involve abnormal, rhythmic discharges of cortical neurons. They are caused by either physiological or psychological conditions...

 are quite common and these types of seizures will not have any response to an antiepileptic drug. In epilepsy an area of the cortex is typically hyperirritable that can often be confirmed by completing an EEG. Antiepileptic drugs function to help reduce this area of irritability and thus prevent epileptiform seizures.

The major molecular targets of marketed anticonvulsant drugs are voltage-gated sodium channels and components of the GABA
Gamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...

 system, including GABAA receptors, the GAT-1 GABA transporter, and GABA transaminase. Additional targets include voltage-gated calcium channels, SV2A
SV2A
Synaptic vesicle glycoprotein 2A is a ubiquitous synaptic vesicle protein that in humans is encoded by the SV2A gene. The protein is targeted by the anti-epileptic drug levetiracetam.-Further reading:...

, and α2δ. The drug class was the US's 5th-best-selling in 2007.

Some anticonvulsants have shown antiepileptogenic effects in animal models of epilepsy. That is, they either prevent the expected development of epilepsy or can halt or reverse the progression of epilepsy. However, no drug has been shown to prevent epileptogenesis
Epileptogenesis
Epileptogenesis is a process by which a normal brain develops epilepsy, a chronic condition in which seizures occur. The process, which is gradual, occurs in symptomatic epilepsy, in which seizures are caused by an identifiable lesion in the brain. It results from acute brain insults such as...

 (the development of epilepsy after an injury such as a head injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...

) in human trials.

Approval


The usual method of achieving approval for a drug is to show it is effective when compared against placebo, or that it is more effective than an existing drug. In monotherapy (where only one drug is taken) it is considered unethical by most to conduct a trial with placebo on a new drug of uncertain efficacy. This is because untreated epilepsy leaves the patient at significant risk of death. Therefore, almost all new epilepsy drugs are initially approved only as adjunctive (add-on) therapies. Patients whose epilepsy is currently uncontrolled by their medication (i.e., it is refractory to treatment) are selected to see if supplementing the medication with the new drug leads to an improvement in seizure control. Any reduction in the frequency of seizures is compared against a placebo.

Once there is confidence that a drug is likely to be effective in monotherapy, trials are conducted where the drug is compared to an existing standard. For partial-onset seizures, this is typically carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...

. Despite the launch of over ten drugs since 1990, no new drug has been shown to be more effective than the older set, which includes carbamazepine, valproate and phenytoin. The lack of superiority over existing treatment, combined with lacking placebo-controlled trials, means that few modern drugs have earned FDA approval as initial monotherapy. In contrast, Europe only requires equivalence to existing treatments, and has approved many more. Despite their lack of FDA approval, the American Academy of Neurology
American Academy of Neurology
The American Academy of Neurology is a professional society for neurologists and neuroscientists. As a medical specialty society it was established in 1949 by A.B. Baker of the University of Minnesota to advance the art and science of neurology, and thereby promote the best possible care for...

 and the American Epilepsy Society still recommend a number of these new drugs as initial monotherapy.

Drugs



In the following list, the dates in parentheses are the earliest approved use of the drug.

Aldehydes


  • Paraldehyde
    Paraldehyde
    Paraldehyde is the cyclic trimer of acetaldehyde molecules. Formally, it is a derivative of 1,3,5-trioxane. The corresponding tetramer is metaldehyde. A colourless liquid, it is sparingly soluble in water and highly soluble in alcohol. Paraldehyde slowly oxidizes in air, turning brown and producing...

     (1882). One of the earliest anticonvulsants. Still used to treat status epilepticus
    Status epilepticus
    Status epilepticus is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 5 minutes, or recurrent seizures without regaining consciousness between seizures...

    , particularly where there are no resuscitation facilities.

Aromatic allylic alcohols

  • Stiripentol
    Stiripentol
    Stiripentol is an anticonvulsant drug used in the treatment of epilepsy. It is unrelated to other anticonvulsants and belongs to the group of aromatic allylic alcohols.-Mechanism of action:...

     (2001 - limited availability). Indicated for the treatment of severe myoclonic epilepsy in infancy (SMEI).

Barbiturates



Barbiturate
Barbiturate
Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...

s are drugs
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...

 that act as central nervous system (CNS) depressant
Depressant
A depressant, or central depressant, is a drug or endogenous compound that depresses the function or activity of a specific part of the brain...

s, and by virtue of this they produce a wide spectrum of effects, from mild sedation
Sedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...

 to anesthesia
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...

. The following are classified
ATC code N03
-N03AA Barbiturates and derivatives:-N03AA Barbiturates and derivatives:-N03AA Barbiturates and derivatives::N03AA01 Methylphenobarbital:N03AA02 Phenobarbital:N03AA03 Primidone:N03AA04 Barbexaclone:N03AA30 Metharbital-N03AB Hydantoin derivatives:...

 as anticonvulsants:
  • Phenobarbital
    Phenobarbital
    Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...

     (1912). See also the related drug primidone
    Primidone
    Primidone is an anticonvulsant of the pyrimidinedione class, the active metabolites of which, phenobarbital and phenylethylmalonamide , are also anticonvulsants...

    .
  • Methylphenobarbital
    Methylphenobarbital
    Methylphenobarbital , also known as mephobarbital and mephobarbitone , marketed under brand names such as Mebaral, Mephyltaletten, Phemiton, and Prominal, is a drug which is a barbiturate derivative and is used primarily as an anticonvulsant, but also as a sedative and anxiolytic...

     (1935). Known as mephobarbital in the US. No longer marketed in the UK
  • Metharbital
    Metharbital
    Metharbital was patented in 1905 by Emil Fischer working for Merck. It was marketed as Gemonil by Abbott Laboratories. It is a barbiturate anticonvulsant, used in the treatment of epilepsy...

     (1952). No longer marketed in the UK or US.
  • Barbexaclone
    Barbexaclone
    Barbexaclone is a salt compound of phenobarbital and levopropylhexedrine. It was introduced in 1983. It has been reported to be as effective as phenobarbital but better tolerated; however, as of 2004, these "promising results" had not yet been confirmed nor denied in controlled trials...

     (1982). Only available in some European countries.


Phenobarbital was the main anticonvulsant from 1912 till the development of phenytoin in 1938. Today, phenobarbital is rarely used to treat epilepsy in new patients since there are other effective drugs that are less sedating. Phenobarbital sodium injection can be used to stop acute convulsions or status epilepticus
Status epilepticus
Status epilepticus is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 5 minutes, or recurrent seizures without regaining consciousness between seizures...

, but a benzodiazepine such as lorazepam, diazepam or midazolam is usually tried first. Other barbiturates only have an anticonvulsant effect at anaesthetic doses.

Benzodiazepines



The benzodiazepines are a class of drugs
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...

 with hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...

, anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...

, anticonvulsive, amnestic
Amnesia
Amnesia is a condition in which one's memory is lost. The causes of amnesia have traditionally been divided into categories. Memory appears to be stored in several parts of the limbic system of the brain, and any condition that interferes with the function of this system can cause amnesia...

 and muscle relaxant
Muscle relaxant
A muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics...

 properties. Benzodiazepines act as a central nervous system depressant. The relative strength of each of these properties in any given benzodiazepine varies greatly and influences the indications for which it is prescribed. Long-term use can be problematic due to the development of tolerance to the anticonvulsant effects and dependency
Substance use disorder
Substance use disorders include substance abuse and substance dependence. In DSM-IV, the conditions are formally diagnosed as one or the other, but it has been proposed that DSM-5 combine the two into a single condition called "Substance-use disorder"....

. Of the many drugs in this class, only a few are used to treat epilepsy:
  • Clobazam
    Clobazam
    Clobazam , is a drug which is a benzodiazepine derivative. It has been marketed as an anxiolytic since 1975 and an anticonvulsant since 1984...

     (1979). Notably used on a short-term basis around menstruation in women with catamenial epilepsy
    Catamenial epilepsy
    Catamenial epilepsy is a subtype of epilepsy, which is a chronic neurological condition characterized by recurrent seizures. Catamenial epilepsy is a subset of this population, which includes women of whom their seizure exacerbation is aligned with their menstrual cycle. Women with catamenial...

    .
  • Clonazepam
    Clonazepam
    Clonazepamis a benzodiazepine drug having anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties. It is marketed by Roche under the trade name Klonopin in the United States and Rivotril in Australia, Brazil, Canada and Europe...

     (1974).
  • Clorazepate
    Clorazepate
    Clorazepate , also known as clorazepate dipotassium, is a drug that is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative, hypnotic and skeletal muscle relaxant properties. Clorazepate is a prodrug for desmethyldiazepam, which is rapidly produced as an active metabolite...

     (1972).


The following benzodiazepines are used to treat status epilepticus
Status epilepticus
Status epilepticus is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 5 minutes, or recurrent seizures without regaining consciousness between seizures...

:
  • Diazepam
    Diazepam
    Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...

     (1963). Can be given rectally by trained care-givers.
  • Midazolam
    Midazolam
    Midazolam is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic,...

     (N/A). Increasingly being used as an alternative to diazepam. This water-soluble drug is squirted into the side of the mouth but not swallowed. It is rapidly absorbed by the buccal mucosa.
  • Lorazepam
    Lorazepam
    Lorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...

     (1972). Given by injection in hospital.


Nitrazepam
Nitrazepam
Nitrazepam is a type of benzodiazepine drug and is marketed in English-speaking countries under the following brand names: Alodorm, Arem, Insoma, Mogadon, Nitrados, Nitrazadon, Ormodon, Paxadorm, Remnos, and Somnite...

, temazepam
Temazepam
Temazepam is an intermediate-acting 3-hydroxy benzodiazepine. It is mostly prescribed for the short-term treatment of sleeplessness in patients who have difficulty maintaining sleep...

, and especially nimetazepam
Nimetazepam
Nimetazepam is an intermediate-acting hypnotic drug which is a benzodiazepine derivative. It was first synthesized by a team at Hoffmann-La Roche in 1962. It possesses hypnotic, anxiolytic, sedative, and skeletal muscle relaxant properties. Nimetazepam is also an anticonvulsant. It is sold in 5 mg...

 are powerful anticonvulsant agents, however their use is rare due to an increased incidence of side effects and strong sedative and motor-impairing properties.

Bromides


  • Potassium bromide
    Potassium bromide
    Potassium bromide is a salt, widely used as an anticonvulsant and a sedative in the late 19th and early 20th centuries, with over-the-counter use extending to 1975 in the United States. Its action is due to the bromide ion...

     (1857). The earliest effective treatment for epilepsy. There would not be a better drug until phenobarbital in 1912. It is still used as an anticonvulsant for dogs and cats.

Carbamates


  • Felbamate
    Felbamate
    Felbamate is an anticonvulsant drug used in the treatment of epilepsy. It is used to treat partial seizures in adults and partial and generalized seizures associated with Lennox-Gastaut syndrome in children...

     (1993). This effective anticonvulsant has had its usage severely restricted due to rare but life-threatening side effects.

Carboxamides




The following are carboxamides:
  • Carbamazepine
    Carbamazepine
    Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...

     (1963). A popular anticonvulsant that is available in generic formulations.
  • Oxcarbazepine
    Oxcarbazepine
    Oxcarbazepine is a anticholinergic anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy. It is also used to treat anxiety and mood disorders, and benign motor tics...

     (1990). A derivative of carbamazepine that has similar efficacy but is better tolerated and is also available generically.
  • Eslicarbazepine acetate
    Eslicarbazepine acetate
    Eslicarbazepine acetate is an antiepileptic drug. It is a prodrug which is activated to eslicarbazepine , an active metabolite of oxcarbazepine....

     (2009)

Fatty acids



The following are fatty-acids:
  • The valproates
    Valproic acid
    Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia...

     — valproic acid
    Valproic acid
    Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia...

    , sodium valproate
    Sodium valproate
    Sodium valproate or valproate sodium is the sodium salt of valproic acid and is an anticonvulsant used in the treatment of epilepsy, anorexia nervosa, panic attack, anxiety disorder, posttraumatic stress disorder, migraine and bipolar disorder, as well as other psychiatric conditions requiring...

    , and divalproex sodium (1967).
  • Vigabatrin
    Vigabatrin
    Vigabatrin is an antiepileptic drug that inhibits the catabolism of gamma-aminobutyric acid by irreversibly inhibiting GABA transaminase. It is an analog of GABA, but it is not a receptor agonist...

     (1989).
  • Progabide
    Progabide
    Progabide is an analog and prodrug of gamma-aminobutyric acid used in the treatment of epilepsy...

  • Tiagabine
    Tiagabine
    Tiagabine -Indications:Tiagabine is approved by U.S. Food and Drug Administration as an adjunctive treatment for partial seizures in ages 12 and up. It may also be prescribed to treat anxiety disorders and neuropathic pain . For anxiety and neuropathic pain, tiagabine is used primarily to augment...

     (1996).


Vigabatrin and progabide are also analogs of GABA.

Hydantoins



The following are hydantoins:
  • Ethotoin
    Ethotoin
    Ethotoin is an anticonvulsant drug used in the treatment of epilepsy. It is a hydantoin, similar to phenytoin. Ethotoin lacks phenytoin's side effects of gingival hyperplasia and hirsutism, however it is less effective. This, combined with the need for frequent dosing has limited its usefulness...

     (1957).
  • Phenytoin
    Phenytoin
    Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...

     (1938).
  • Mephenytoin
    Mephenytoin
    Mephenytoin is a hydantoin, used as an anticonvulsant. It was introduced approximately 10 years after phenytoin, in the late 1940s. The significant metabolite of mephenytoin is nirvanol , which was the first hydantoin...

  • Fosphenytoin
    Fosphenytoin
    Fosphenytoin is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures....

     (1996).

Oxazolidinediones



The following are oxazolidinediones:
  • Paramethadione
    Paramethadione
    Paramethadione is an anticonvulsant in the oxazolidinedione class. It is associated with fetal trimethadione syndrome, which is also known as paramethadione syndrome.-Chemistry:...

  • Trimethadione
    Trimethadione
    Trimethadione is an oxazolidinedione anticonvulsant. It is most commonly used to treat epileptic conditions that are resistant to other treatments.-Fetal trimethadione syndrome:...

     (1946).
  • Ethadione
    Ethadione
    Ethadione is an anticonvulsant medication in the oxazolidinedione family used mainly to treat seizures and meretrixitus....


Pyrrolidines


  • Brivaracetam
    Brivaracetam
    Brivaracetam, the 4-n-propyl analog of levetiracetam, is a racetam derivative with anticonvulsant properties. Brivaracetam is believed to act by binding to the ubiquitous synaptic vesicle protein SV2. Phase II clinical trials in adult patients with refractory partial seizures were promising...

  • Levetiracetam (1999).
  • Seletracetam
    Seletracetam
    Seletracetam is a drug of the racetam family. It is currently being developed by UCB Pharmaceuticals as an anticonvulsant drug. While similar in structure to so-called nootropic drugs, it is not expected to have cognitive enhancing properties....


Succinimides



The following are succinimides:
  • Ethosuximide
    Ethosuximide
    Ethosuximide is a succinimide anticonvulsant, used mainly in absence seizures.-Approved:It is approved for absence seizures. Ethosuximide is considered the first choice drug for treating absence seizures in part because it lacks the idiosyncratic hepatotoxicity of the alternative anti-absence...

     (1955).
  • Phensuximide
    Phensuximide
    Phensuximide is an anticonvulsant in the succinimide class.-Chemistry:Phensuximide, 1-methyl-3-phenylpyrrolidine-2,5-dione is synthesized by the reaction of phenylsuccinic acid or its anhydride with methylamine.*C.A. Miller, L.M. Long, ....

  • Mesuximide
    Mesuximide
    Mesuximide is an succinimide anticonvulsant medication. It is sold as a racemate by Pfizer under the tradenames Petinutin and Celontin...


Sulfonamides


  • Acetazolamide
    Acetazolamide
    Acetazolamide, sold under the trade name Diamox, is a carbonic anhydrase inhibitor that is used to treat glaucoma, epileptic seizures, Idiopathic intracranial hypertension , altitude sickness, cystinuria, and dural ectasia...

     (1953).
  • Sultiame
  • Methazolamide
    Methazolamide
    Methazolamide is a carbonic anhydrase inhibitor....

  • Zonisamide
    Zonisamide
    Zonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures for adults; infantile spasm, mixed seizure types of Lennox-Gastaut syndrome, myoclonic, and generalized tonic clonic seizure.-History:...

     (2000).

Valproylamides (amide derivatives of valproate)


  • Valpromide
    Valpromide
    Valpromide is a carboxamide derivative of valproic acid used in the treatment of epilepsy and some affective disorders. It is rapidly metabolised to valproic acid but has anticonvulsant properties itself...

  • Valnoctamide
    Valnoctamide
    Valnoctamide has been used in France as a sedative-hypnotic since 1964. It is a structural isomer of valpromide, a valproic acid prodrug; unlike valpromide, however, valnoctamide is not transformed into its homologous acid, valnoctic acid, in vivo.-Indications:In addition to being a sedative,...


Non-medical anticonvulsants



Sometimes, ketogenic diet
Ketogenic diet
The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control epilepsy in children. The diet mimics aspects of starvation by forcing the body to burn fats rather than carbohydrates...

 or vagus nerve stimulation
Vagus nerve stimulation
Vagus nerve stimulation is an adjunctive treatment for certain types of intractable epilepsy and treatment-resistant depression.- Mechanism of action :...

 are described as "anticonvulsant" therapies as well.

Treatment guidelines


According to guidelines by the AAN
American Academy of Neurology
The American Academy of Neurology is a professional society for neurologists and neuroscientists. As a medical specialty society it was established in 1949 by A.B. Baker of the University of Minnesota to advance the art and science of neurology, and thereby promote the best possible care for...

 and AES, mainly based on a major article review in 2004, patients with newly diagnosed epilepsy who require treatment can be initiated on standard anticonvulsants such as carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...

, phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...

, valproic acid
Valproic acid
Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia...

/valproate semisodium
Valproate semisodium
Valproate semisodium or divalproex sodium consists of a compound of sodium valproate and valproic acid in a 1:1 molar relationship in an enteric coated form. It is used in the United Kingdom, Canada, and United States for the treatment of the manic episodes of bipolar disorder...

, phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...

, or on the newer anticonvulsants gabapentin
Gabapentin
Gabapentin is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the treatment of epilepsy, and currently is also used to relieve neuropathic pain...

, lamotrigine
Lamotrigine
Lamotrigine, marketed in the US and most of Europe as Lamictal by GlaxoSmithKline, is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. It is also used as an adjunct in treating depression, though this is considered off-label usage...

, oxcarbazepine
Oxcarbazepine
Oxcarbazepine is a anticholinergic anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy. It is also used to treat anxiety and mood disorders, and benign motor tics...

 or topiramate
Topiramate
Topiramate is an anticonvulsant drug. It was originally produced by Ortho-McNeil Neurologics and Noramco, Inc., both divisions of the Johnson & Johnson Corporation. This medication was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil...

. The choice of anticonvulsants depends on individual patient characteristics. Both newer and older drugs are generally equally effective in new onset epilepsy. The newer drugs tend to have fewer side effects. For newly diagnosed partial or mixed seizures, there is evidence for using gabapentin, lamotrigine, oxcarbazepine or topiramate as monotherapy. Lamotrigine
Lamotrigine
Lamotrigine, marketed in the US and most of Europe as Lamictal by GlaxoSmithKline, is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. It is also used as an adjunct in treating depression, though this is considered off-label usage...

 can be included in the options for children with newly diagnosed absence seizures.

History


The first anticonvulsant was bromide
Bromide
A bromide is a chemical compound containing bromide ion, that is bromine atom with effective charge of −1. The class name can include ionic compounds such as caesium bromide or covalent compounds such as sulfur dibromide.-Natural occurrence:...

, suggested in 1857 by Charles Locock who used it to treat women with "hysterical epilepsy" (probably catamenial epilepsy). Potassium bromide was also noted to cause impotence in men. Authorities concluded that potassium bromide would dampen sexual excitement thought to cause the seizures. In fact, bromides were effective against epilepsy, and also caused impotence; it is now known that impotence is a side effect of bromide treatment, which is not related to its anti-epileptic effects. It also suffered from the way it affected behaviour, introducing the idea of the 'epileptic personality' which was actually a result of the medication. Phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...

 was first used in 1912 for both its sedative and antiepileptic properties. By the 1930s, the development of animal models in epilepsy research led to the development of phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...

 by Tracy Putnam and H. Houston Merritt
H. Houston Merritt
H. Houston Merritt was one of the pre-eminent academic neurologists of his day. As the chair of the Neurological Institute of New York from 1948 to 1967, he oversaw the training of hundreds of neurologists; 35 of his former students have become chairs of academic neurology departments across the...

, which had the distinct advantage of treating epileptic seizures with less sedation. By the 1970s, an National Institutes of Health initiative, the Anticonvulsant Screening Program, headed by J. Kiffin Penry, served as a mechanism for drawing the interest and abilities of pharmaceutical companies in the development of new anticonvulsant medications.

Marketing approval history


The following table lists anticonvulsant drugs together with the date their marketing was approved in the US, UK and France. Data for the UK and France are incomplete. In recent years, the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...

 has approved drugs throughout the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...

. Some of the drugs are no longer marketed.
DrugBrandUSUKFrance
acetazolamide
Acetazolamide
Acetazolamide, sold under the trade name Diamox, is a carbonic anhydrase inhibitor that is used to treat glaucoma, epileptic seizures, Idiopathic intracranial hypertension , altitude sickness, cystinuria, and dural ectasia...

Diamox 1953-07-2727 July 1953 1988
carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...

Tegretol 1974-07-1515 July 1974 1965 1963
clobazam
Clobazam
Clobazam , is a drug which is a benzodiazepine derivative. It has been marketed as an anxiolytic since 1975 and an anticonvulsant since 1984...

Frisium 1979
clonazepam
Clonazepam
Clonazepamis a benzodiazepine drug having anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties. It is marketed by Roche under the trade name Klonopin in the United States and Rivotril in Australia, Brazil, Canada and Europe...

Klonopin/Rivotril 1975-06-044 June 1975 1974
diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...

Valium 1963-11-1515 November 1963
divalproex sodium Depakote 1983-03-1010 March 1983
ethosuximide
Ethosuximide
Ethosuximide is a succinimide anticonvulsant, used mainly in absence seizures.-Approved:It is approved for absence seizures. Ethosuximide is considered the first choice drug for treating absence seizures in part because it lacks the idiosyncratic hepatotoxicity of the alternative anti-absence...

Zarontin 1960-11-022 November 1960 1955 1962
ethotoin
Ethotoin
Ethotoin is an anticonvulsant drug used in the treatment of epilepsy. It is a hydantoin, similar to phenytoin. Ethotoin lacks phenytoin's side effects of gingival hyperplasia and hirsutism, however it is less effective. This, combined with the need for frequent dosing has limited its usefulness...

Peganone 1957-04-2222 April 1957
felbamate
Felbamate
Felbamate is an anticonvulsant drug used in the treatment of epilepsy. It is used to treat partial seizures in adults and partial and generalized seizures associated with Lennox-Gastaut syndrome in children...

Felbatol 1993-07-2929 July 1993
fosphenytoin
Fosphenytoin
Fosphenytoin is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures....

Cerebyx 1996-08-055 August 1996
gabapentin
Gabapentin
Gabapentin is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the treatment of epilepsy, and currently is also used to relieve neuropathic pain...

Neurontin 1993-12-3030 December 1993 1993-05May 1993 1994-10October 1994
lamotrigine
Lamotrigine
Lamotrigine, marketed in the US and most of Europe as Lamictal by GlaxoSmithKline, is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. It is also used as an adjunct in treating depression, though this is considered off-label usage...

Lamictal 1994-12-2727 December 1994 1991-10October 1991 1995-05May 1995
lacosamide
Lacosamide
Lacosamide is a medication developed by UCB for the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain marketed under the trade name Vimpat....

Vimpat
levetiracetam Keppra 1999-11-3030 November 1999 2000-09-2929 September 2000 2000-09-2929 September 2000
mephenytoin
Mephenytoin
Mephenytoin is a hydantoin, used as an anticonvulsant. It was introduced approximately 10 years after phenytoin, in the late 1940s. The significant metabolite of mephenytoin is nirvanol , which was the first hydantoin...

Mesantoin 1946-10-2323 October 1946
metharbital
Metharbital
Metharbital was patented in 1905 by Emil Fischer working for Merck. It was marketed as Gemonil by Abbott Laboratories. It is a barbiturate anticonvulsant, used in the treatment of epilepsy...

Gemonil 1952
methsuximide Celontin 1957-02-088 February 1957
methazolamide
Methazolamide
Methazolamide is a carbonic anhydrase inhibitor....

Neptazane 1959-01-2626 January 1959
oxcarbazepine
Oxcarbazepine
Oxcarbazepine is a anticholinergic anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy. It is also used to treat anxiety and mood disorders, and benign motor tics...

Trileptal 2000-01-1414 January 2000 2000
phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...

1912 1920
phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...

Dilantin/Epanutin 1938 1938 1941
phensuximide
Phensuximide
Phensuximide is an anticonvulsant in the succinimide class.-Chemistry:Phensuximide, 1-methyl-3-phenylpyrrolidine-2,5-dione is synthesized by the reaction of phenylsuccinic acid or its anhydride with methylamine.*C.A. Miller, L.M. Long, ....

Milontin 1953
pregabalin
Pregabalin
Pregabalin is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults. It has also been found effective for generalized anxiety disorder and is approved for this use in the European Union. It was designed...

Lyrica 2004-12-3030 December 2004 2004-07-066 July 2004 2004-07-066 July 2004
primidone
Primidone
Primidone is an anticonvulsant of the pyrimidinedione class, the active metabolites of which, phenobarbital and phenylethylmalonamide , are also anticonvulsants...

Mysoline 1954-03-088 March 1954 1952 1953
sodium valproate
Sodium valproate
Sodium valproate or valproate sodium is the sodium salt of valproic acid and is an anticonvulsant used in the treatment of epilepsy, anorexia nervosa, panic attack, anxiety disorder, posttraumatic stress disorder, migraine and bipolar disorder, as well as other psychiatric conditions requiring...

Epilim 1977-12December 1977 1967-06June 1967
stiripentol
Stiripentol
Stiripentol is an anticonvulsant drug used in the treatment of epilepsy. It is unrelated to other anticonvulsants and belongs to the group of aromatic allylic alcohols.-Mechanism of action:...

Diacomit 2001-12-055 December 2001 2001-12-055 December 2001
tiagabine
Tiagabine
Tiagabine -Indications:Tiagabine is approved by U.S. Food and Drug Administration as an adjunctive treatment for partial seizures in ages 12 and up. It may also be prescribed to treat anxiety disorders and neuropathic pain . For anxiety and neuropathic pain, tiagabine is used primarily to augment...

Gabitril 1997-09-3030 September 1997 1998 1997-11November 1997
topiramate
Topiramate
Topiramate is an anticonvulsant drug. It was originally produced by Ortho-McNeil Neurologics and Noramco, Inc., both divisions of the Johnson & Johnson Corporation. This medication was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil...

Topamax 1996-12-2424 December 1996 1995
trimethadione
Trimethadione
Trimethadione is an oxazolidinedione anticonvulsant. It is most commonly used to treat epileptic conditions that are resistant to other treatments.-Fetal trimethadione syndrome:...

Tridione 1946-01-2525 January 1946
valproic acid
Valproic acid
Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia...

Depakene/Convulex 1978-02-2828 February 1978 1993
vigabatrin
Vigabatrin
Vigabatrin is an antiepileptic drug that inhibits the catabolism of gamma-aminobutyric acid by irreversibly inhibiting GABA transaminase. It is an analog of GABA, but it is not a receptor agonist...

Sabril 2009-08-2121 August 2009 1989
zonisamide
Zonisamide
Zonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures for adults; infantile spasm, mixed seizure types of Lennox-Gastaut syndrome, myoclonic, and generalized tonic clonic seizure.-History:...

Zonegran 2000-03-2727 March 2000 2005-03-1010 March 2005 2005-03-1010 March 2005

Use in pregnancy


During pregnancy, the metabolism of several anticonvulsants is affected. There may be an increase in the clearance and resultant decrease in the blood concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. Therefore, these drugs should be monitored during use in pregnancy.
Taking valproic acid or divalproex sodium during pregnancy should be cautioned against, as this class of medications has been linked to birth defects (teratogenic).

There is inadequate evidence to determine if newborns of women with epilepsy taking anticonvulsants have a substantially increased risk of hemorrhagic disease of the newborn.

Regarding breastfeeding
Breastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...

, some anticonvulsants probably pass into breast milk
Breast milk
Breast milk, more specifically human milk, is the milk produced by the breasts of a human female for her infant offspring...

in clinically significant amounts, including primidone and levetiracetam. On the other hand, valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts.

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